Lactobacillus Reuteri in Treatment of Functional Abdominal Pain and Chronic Constipation in Children

NCT01587846 | Unknown Phase 3

• 1 other identifier: LR-2012-KL
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Beneficial therapeutic effect of probiotics has been reported in children with irritable bowel syndrome, but not consistently in other functional gastrointestinal disorders. Although there is evidence that probiotics increase stool frequency and decrease stool consistency in healthy individuals the evidence for efficacy in constipation is limited. Children with functional abdominal pain (FAP) and constipation will be included in the study. Children with FAP will be randomized in one of two groups and will receive either L. reuteri in a daily dose of 108 CFU, or placebo during three months. Children with chronic constipation will receive either L. reuteri in a daily dose of 108 CFU and lactulose, or placebo and lactulose. Frequency and intensity of episodes of abdominal pain during and after intervention will be recorded in children with FAP. Frequency of defecation, stool consistency and need for lactulose will be recorded in children with chronic constipation.

Conditions

Abdominal Pain; Constipation - Functional

Keywords

abdominal pain, constipation, Lactobacillus reuteri

Outcome Measures

Primary Outcomes (2)

• Intensity of abdominal pain

  Pain score on visual-analogue scale during treatment

  3 months

• Severity of chronic constipation

  Stool consistency score on Bristol stool scale during treatment

  3 months

Secondary Outcomes (2)

• Intensity of abdominal pain after treatment

  1 month

• Severity of chronic constipation after treatment

  1 month

Study Arms (4)

Probiotic/abdominal pain

EXPERIMENTAL

Children with functional abdominal pain that will receive probiotic.

Dietary Supplement: Administration of L.reuteri in children with abdominal pain

Placebo/abdominal pain

EXPERIMENTAL

Children with functional abdominal pain that will receive placebo.

Dietary Supplement: Administration of placebo in children with abdominal pain

Probiotic/constipation

EXPERIMENTAL

Children with chronic constipation tha will receive probiotic plus lactulose

Dietary Supplement: Administration of L.reuteri in children with constipation

Placebo/chronic constipation

EXPERIMENTAL

Children with chronic constipation that will receive placebo plus lactulose

Dietary Supplement: Administration of placebo in children with constipation

Interventions

Administration of L.reuteri in children with abdominal pain DIETARY_SUPPLEMENT

Group of around 75 children which will receive L. reuteri at a dose 100.000.000 CFU per dose for 3 months. The active study product consists of a citrus flavored 450 mg chewable tablet containing freeze-dried L. reuteri DSM 17938. The study product is a convex tablet 10.3 mm in diameter, plain on both sides and with faint spots. It is composed of freeze-dried L. reuteri, isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon-lime flavoring and anhydrous citric acid. The total viable count of L. reuteri is 1x100.000.000 live bacteria (CFU)/tablet.

Probiotic/abdominal pain

Administration of placebo in children with abdominal pain DIETARY_SUPPLEMENT

Group of around 75 children which will receive placebo for 3 months. The placebo consists of a citrus flavored 450 mg chewable convex tablet 10.3 mm in diameter, plain on both sides and with faint spots. It is composed of isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon-lime flavoring and anhydrous citric acid.

Placebo/abdominal pain

Administration of L.reuteri in children with constipation DIETARY_SUPPLEMENT

Group of around 75 children which will receive L. reuteri at a dose 100.000.000 CFU per dose plus lactulose in a dose 1-3 ml/kg, according to the stool frequency and consistency, for 3 months. The active study product consists of a citrus flavored 450 mg chewable tablet containing freeze-dried L. reuteri DSM 17938. The study product is a convex tablet 10.3 mm in diameter, plain on both sides and with faint spots. It is composed of freeze-dried L. reuteri, isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon-lime flavoring and anhydrous citric acid. The total viable count of L. reuteri is 1x100.000.000 live bacteria (CFU)/tablet.

Probiotic/constipation

Administration of placebo in children with constipation DIETARY_SUPPLEMENT

Group of around 75 children which will receive placebo plus lactulose in a dose 1-3 ml/kg, according to the stool frequency and consistency, for 3 months. The placebo study product consists of a citrus flavored 450 mg chewable convex tablet 10.3 mm in diameter, plain on both sides and with faint spots. It is composed of isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon-lime flavoring and anhydrous citric acid.

Placebo/chronic constipation

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children with functional abdominal pain (age 4-18 years)
• Children with chronic constipation (age 2-18 years)

You may not qualify if:

• Immunodeficiency
• Receiving probiotic and/or prebiotic products 7 days prior to enrolment
• Neoplasms
• Chronic disorders
• Presence of "red flags":
• Weight loss of more than 10%
• Growth retardation or growth failure
• Extraintestinal symptoms (fever, rash, joint pain, aphthae, affection of the urinary system)
• Frequent vomiting
• Abnormalities in laboratory findings (anemia, elevated ESR)
• Abnormalities in clinical findings (organomegaly, perianal disease)

Sponsors & Collaborators

• Sisters of Mercy University Hospital: lead
• BioGaia AB: collaborator

Study Sites (1)

University Hospital Centre "Sisters of Mercy"

Zagreb, 10000, Croatia

RECRUITING

Related Publications (10)

• Savino F, Cordisco L, Tarasco V, Palumeri E, Calabrese R, Oggero R, Roos S, Matteuzzi D. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-controlled trial. Pediatrics. 2010 Sep;126(3):e526-33. doi: 10.1542/peds.2010-0433. Epub 2010 Aug 16.

  PMID: 20713478 BACKGROUND

• Coccorullo P, Strisciuglio C, Martinelli M, Miele E, Greco L, Staiano A. Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation: a double-blind, randomized, placebo-controlled study. J Pediatr. 2010 Oct;157(4):598-602. doi: 10.1016/j.jpeds.2010.04.066. Epub 2010 Jun 12.

  PMID: 20542295 BACKGROUND

• Szajewska H. Probiotics and functional gastrointestinal disorders. J Pediatr Gastroenterol Nutr. 2011 Dec;53 Suppl 2:S30-2. No abstract available.

  PMID: 22235462 BACKGROUND

• Tabbers MM, Chmielewska A, Roseboom MG, Crastes N, Perrin C, Reitsma JB, Norbruis O, Szajewska H, Benninga MA. Fermented milk containing Bifidobacterium lactis DN-173 010 in childhood constipation: a randomized, double-blind, controlled trial. Pediatrics. 2011 Jun;127(6):e1392-9. doi: 10.1542/peds.2010-2590. Epub 2011 May 23.

  PMID: 21606153 BACKGROUND

• Horvath A, Dziechciarz P, Szajewska H. Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood. Aliment Pharmacol Ther. 2011 Jun;33(12):1302-10. doi: 10.1111/j.1365-2036.2011.04665.x. Epub 2011 Apr 20.

  PMID: 21507030 BACKGROUND

• Chmielewska A, Szajewska H. Systematic review of randomised controlled trials: probiotics for functional constipation. World J Gastroenterol. 2010 Jan 7;16(1):69-75. doi: 10.3748/wjg.v16.i1.69.

  PMID: 20039451 BACKGROUND

• Gawronska A, Dziechciarz P, Horvath A, Szajewska H. A randomized double-blind placebo-controlled trial of Lactobacillus GG for abdominal pain disorders in children. Aliment Pharmacol Ther. 2007 Jan 15;25(2):177-84. doi: 10.1111/j.1365-2036.2006.03175.x.

  PMID: 17229242 BACKGROUND

• Szajewska H, Setty M, Mrukowicz J, Guandalini S. Probiotics in gastrointestinal diseases in children: hard and not-so-hard evidence of efficacy. J Pediatr Gastroenterol Nutr. 2006 May;42(5):454-75. doi: 10.1097/01.mpg.0000221913.88511.72.

  PMID: 16707966 BACKGROUND

• Jadresin O, Sila S, Trivic I, Misak Z, Hojsak I, Kolacek S. Lack of Benefit of Lactobacillus reuteri DSM 17938 as an Addition to the Treatment of Functional Constipation. J Pediatr Gastroenterol Nutr. 2018 Dec;67(6):763-766. doi: 10.1097/MPG.0000000000002134.

  PMID: 30134331 DERIVED

• Jadresin O, Hojsak I, Misak Z, Kekez AJ, Trbojevic T, Ivkovic L, Kolacek S. Lactobacillus reuteri DSM 17938 in the Treatment of Functional Abdominal Pain in Children: RCT Study. J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):925-929. doi: 10.1097/MPG.0000000000001478.

  PMID: 27906800 DERIVED

MeSH Terms

Conditions

Abdominal Pain; Constipation

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive

Study Officials

• Sanja Kolaček, MD, PhD

  Head, Department of Pediatrics, Clinical Professor

  PRINCIPAL INVESTIGATOR

• Iva Hojsak, MD, PhD

  Consultant in Pediatric Gastroenterology

  STUDY DIRECTOR

• Oleg Jadrešin, MD, MSc

  Consultant in Pediatric Gastroenterology

  STUDY CHAIR

Central Study Contacts

Oleg Jadrešin, MD, MSc

CONTACT

00385914600130; oleg.jadresin@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Department of Pediatrics, Clinical Professor, Principal Investigator

Study Record Dates

• First Submitted: April 23, 2012
• First Posted: April 30, 2012
• Study Start: October 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 3, 2012

Record last verified: 2012-10

Locations

CR (1)